Perampanel as monotherapy or first adjunctive therapy in pediatric and adult patients with epilepsy: the first United States-based phase IV open-label ELEVATE study.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3.

Assessment of X-ray shielding properties of polystyrene incorporated with different nano-sizes of PbO.

PbO (lead oxide) particles with different sizes were incorporated into polystyrene (PS) with various weight fractions (0, 10, 15, 25, 35%). These novel PS/PbO nano-composites were produced by roll mill mixing and compressing molding techniques and then investigated for radiation attenuation of X-rays (N-series/ISO 4037) typically used in radiology. Properties of the PbO particles were studied by X-ray diffraction (XRD).

Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission.

Objective: We conducted an abattoir-based cross-sectional study in the five administrative regions of Northern Ghana to determine the distribution of bovine tuberculosis (BTB) among slaughtered carcasses and identify the possibility of zoonotic transmission.

Methods: Direct smear microscopy was done on 438 tuberculosis-like lesions from selected cattle organs and cultured on Lowenstein-Jensen media. Acid-fast bacilli (AFB) isolates were confirmed as members of the Mycobacterium tuberculosis complex (MTBC) by PCR amplification of IS6110 and rpoß.

Platypnoea-orthodeoxia syndrome and hemidiaphragm paralysis.

A woman in her 70s was admitted to hospital with worsening shortness of breath and no prior respiratory history of note. This patient's shortness of breath was posture-dependent; symptoms were markedly worse and oxygen saturations were lower on sitting upright than in recumbency. Her shortness of breath had started several weeks prior to admission and had slowly worsened.

Application of Doehlert experimental design for the removal of radium from aqueous solution by cross-linked phenoxycalix[4]pyrrole-polymer using Ba(II) as a model.

Ra-226 is a naturally occurring radionuclide that is derived from uranium-238 series, and it is present at low concentrations in rocks, soil, and groundwater. Many efforts have been exerted for the decontamination of radium from aqueous media in order to meet the increasing water demand of the population. To this aim, a new polymer based on cross-linked phenoxycalix[4]pyrrole was designed and employed in solid/liquid extractions in order to remove radium from aqueous solutions.

Bioaccessibility of lead in Dittrichia viscosa plants and risk assessment of human exposure around a fertilizer industry in Lebanon.

Total and bioaccessible lead (Pb) concentrations in Dittrichia viscosa and soil samples were considered for estimating the potential health risk, related to both plant intake and accidental soil ingestion by adult and child consumers, near a Lebanese fertilizer plant. A total of 27 plant samples, from 9 uncultivated sites situated around the plant, were analyzed in order to assess the total and bioaccessible Pb content. Physiologically based extraction test (PBET) was used to estimate oral bioaccessibility of Pb in edible plant parts.

Bioaccessibility and radioisotopes of lead in soils around a fertilizer industry in Lebanon.

The use of phosphate ore by fertilizer industries is considered a major source of soil contamination by trace metals and radionuclides. Despite its low mobility and bioavailability, lead (Pb) is among soil contaminants that pose a serious risk to human health. This study evaluates the potential impact of a fertilizer factory in North Lebanon on the total content of Pb and the activity concentration of its radioisotopes in residential, non-agricultural lands around the industry, as well as its mobility and bioaccessibility in soil samples collected at different depths.

Patent Foramen Ovale Closure in 2019.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people it is a benign finding; however, in some the PFO can open widely, enabling a paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed.

Nav1.5 in astrocytes plays a sex-specific role in clinical outcomes in a mouse model of multiple sclerosis.

Astrogliosis is a hallmark of neuroinflammatory disorders such as multiple sclerosis (MS). A detailed understanding of the underlying molecular mechanisms governing astrogliosis might facilitate the development of therapeutic targets. We investigated whether Nav1.

Connectome analysis with diffusion MRI in idiopathic Parkinson's disease: Evaluation using multi-shell, multi-tissue, constrained spherical deconvolution.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects extensive regions of the central nervous system. In this work, we evaluated the structural connectome of patients with PD, as mapped by diffusion-weighted MRI tractography and a multi-shell, multi-tissue (MSMT) constrained spherical deconvolution (CSD) method to increase the precision of tractography at tissue interfaces. The connectome was mapped with probabilistic MSMT-CSD in 21 patients with PD and in 21 age- and gender-matched controls.

Virus-Mediated Knockdown of Nav1.3 in Dorsal Root Ganglia of STZ-Induced Diabetic Rats Alleviates Tactile Allodynia.

Diabetic neuropathic pain affects a substantial number of people and represents a major public health problem. Available clinical treatments for diabetic neuropathic pain remain only partially effective and many of these treatments carry the burden of side effects or the risk of dependence. The misexpression of sodium channels within nociceptive neurons contributes to abnormal electrical activity associated with neuropathic pain.

Impact of a phosphate fertilizer plant on the contamination of marine biota by heavy elements.

Due to their toxicity, persistence, and bioaccumulation, metals are important marine environment pollutants, especially in low renewal rate water such as the Mediterranean Sea, receiving a lot of untreated industrial waste. The impact of a phosphate fertilizer plant on the marine biota metal contamination was studied. Several types of organisms: crabs, mussels, patella and fish were collected from two areas of the Lebanese coast, one subjected to the impact of the plant and another away from it; samples were analyzed for Zn, U, Cr, V, Mn, Ni, Co, Cu, As, Cd and Pb by ICP-MS.

Voltage-gated sodium channel Nav 1.5 contributes to astrogliosis in an in vitro model of glial injury via reverse Na+ /Ca2+ exchange.

Astrogliosis is a prominent feature of many, if not all, pathologies of the brain and spinal cord, yet a detailed understanding of the underlying molecular pathways involved in the transformation from quiescent to reactive astrocyte remains elusive. We investigated the contribution of voltage-gated sodium channels to astrogliosis in an in vitro model of mechanical injury to astrocytes. Previous studies have shown that a scratch injury to astrocytes invokes dual mechanisms of migration and proliferation in these cells.

Genetic control of the segregation of pain-related sensory neurons innervating the cutaneous versus deep tissues.

Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA lineage neurons.

Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis.

Although nearly 11 million individuals yearly require medical treatment due to burn injuries and develop clinically intractable pain, burn injury-induced pain is poorly understood, with relatively few studies in preclinical models. To elucidate mechanisms of burn injury-induced chronic pain, we utilized a second-degree burn model, which produces a persistent neuropathic pain phenotype. Rats with burn injury exhibited reduced mechanical pain thresholds ipsilateral to the burn injury.

Virus-mediated shRNA knockdown of Na(v)1.3 in rat dorsal root ganglion attenuates nerve injury-induced neuropathic pain.

Neuropathic pain is a chronic condition that is often refractory to treatment with available therapies and thus an unmet medical need. We have previously shown that the voltage-gated sodium channel Na(v)1.3 is upregulated in peripheral and central nervous system (CNS) of rats following nerve injury, and that it contributes to nociceptive neuron hyperexcitability in neuropathic conditions.

Maladaptive dendritic spine remodeling contributes to diabetic neuropathic pain.

Diabetic neuropathic pain imposes a huge burden on individuals and society, and represents a major public health problem. Despite aggressive efforts, diabetic neuropathic pain is generally refractory to available clinical treatments. A structure-function link between maladaptive dendritic spine plasticity and pain has been demonstrated previously in CNS and PNS injury models of neuropathic pain.

Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.

Dorsal root ganglia (DRGs) contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions.

Phenotypic switching of nonpeptidergic cutaneous sensory neurons following peripheral nerve injury.

In adult mammals, the phenotype of half of all pain-sensing (nociceptive) sensory neurons is tonically modulated by growth factors in the glial cell line-derived neurotrophic factor (GDNF) family that includes GDNF, artemin (ARTN) and neurturin (NRTN). Each family member binds a distinct GFRα family co-receptor, such that GDNF, NRTN and ARTN bind GFRα1, -α2, and -α3, respectively. Previous studies revealed transcriptional regulation of all three receptors in following axotomy, possibly in response to changes in growth factor availability.

The BMP coreceptor RGMb promotes while the endogenous BMP antagonist noggin reduces neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling.

Repulsive guidance molecule b (RGMb) is a bone morphogenetic protein (BMP) coreceptor and sensitizer of BMP signaling, highly expressed in adult dorsal root ganglion (DRG) sensory neurons. We used a murine RGMb knock-out to gain insight into the physiological role of RGMb in the DRG, and address whether RGMb-mediated modulation of BMP signaling influences sensory axon regeneration. No evidence for altered development of the PNS and CNS was detected in RGMb(-/-) mice.

VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch.

Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown. We generated conditional null mice in which vesicular glutamate transporter type 2 (VGLUT2)-dependent synaptic glutamate release from mainly Nav1.8-expressing nociceptors was abolished.

Characterization of two Runx1-dependent nociceptor differentiation programs necessary for inflammatory versus neuropathic pain.

Background: The cellular and molecular programs that control specific types of pain are poorly understood. We reported previously that the runt domain transcription factor Runx1 is initially expressed in most nociceptors and controls sensory neuron phenotypes necessary for inflammatory and neuropathic pain.

Results: Here we show that expression of Runx1-dependent ion channels and receptors is distributed into two nociceptor populations that are distinguished by persistent or transient Runx1 expression.

Nintendo Wii video-gaming ability predicts laparoscopic skill.

Background: Studies using conventional consoles have suggested a possible link between video-gaming and laparoscopic skill. The authors hypothesized that the Nintendo Wii, with its motion-sensing interface, would provide a better model for laparoscopic tasks. This study investigated the relationship between Nintendo Wii skill, prior gaming experience, and laparoscopic skill.

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1.